Albinism has been recognized in many mammalian species including humans. In man, at least 72 entries are cataloged in Mendelian Inheritance in Man and have been shown to cause various forms of albinism. Albinism is associated with other medical conditions, such as deafness and immunodeficiencies, thus, albinism mutations, which affect melanocyte production and migration, also have pleiotrophic effects that present as vision, auditory and other abnormalities (Brown et al., 1971; Creel et al., 1983; Elekessy et al., 1973; Guillery, 1974; Guillery, 1996; Guillery et al., 1974; Halaban et al., 1988; Leventhal et al., 1985; Weber et al., 1978). Hence, the genes controlling pigmentation play other important physiological roles in mammalian biology besides coloration and potential UV protection.
The domestic cat has at least three loci (dominant white, white spotting, pointing) controlling pigment production that include genes that affect melanocyte production and migration and melanin synthesis. Dominant white, W, affects melanocyte production and is strongly associated with eye color and deafness (Bamber, 1933; Bergsma et al., 1971; Brown et al., 1971). White spotting, S, affects melanocyte migration and produces cats with mainly dorsal pigmentation (Kuhn, 1928; Whiting, 1919). Tentative alleles at the S locus can be expressed as white feet only, white belly or neck spots, or, in the homozygous state, SS, patches of color only near the ears and on the tail. The tyrosinase gene, TYR, which encodes an enzyme required for melanin production in mammals (Halaban et al., 2002; Robinson, 1973) has been implicated for several decades as the gene controlling Siamese “points” (cs). The tyrosinase locus was originally designated the Color locus, C, and was later assigned as the causative gene for temperature sensitive and albinism mutations in several species, excluding the cat.
Albinism variations have been recognized in the domestic cat for several hundred years. The Siamese cat, one of the originally developed cat breeds, has a distinguishing phenotype that is a form of albinism. Siamese cats have a distinctive coat color with pigment only being found on the cooler extremities of the body, producing a “mask” on the face and darkened paws and tail. This type of albinism is commonly referred to as “pointed” or “himalayan” in nonhuman species and has been recognized in rabbits, gerbil and humans (Aigner et al., 2000; Petrij et al., 2001; Tripathi et al., 1991). Since, the causative mutations have been determined or are linked to the gene tyrosinase (TYR) in these other species, the cat phenotypes have also been suggested to be a result of temperature-sensitive mutations at the same gene (Halaban et al., 2002; Kidson et al., 1981; King et al., 1991). A linkage analysis between the Siamese “pointed” phenotype and protein polymorphisms in hemoglobin, HBB, which is closely linked to TYR, also supported this conclusion (O'Brien et al., 1986). At that time, linkage had been shown between HBB and TYR in various species, but only proven to be syntenic in the cat via a somatic cell hybrid panel (O'Brien et al., 1997 and Rinchik et al., 1993), but the Siamese and Burmese phenotype mutations in cats were not been previously determined, nor were albino cats definitively been proven to be a mutation of the TYR albinism series.
Cats have been proven to have an allelic series with at least three alleles, C>cb>, cs (Thompson, 1943; Tjebbes, 1942). These three alleles produce four phenotypes: C allele is completely dominant with normal color presentation; the Burmese phenotypic variant, cbcb, expresses as sable coloration throughout the body and extremities, although all pigment is black (eumelanin); the Siamese phenotypic variant; cscs, is the “pointed” coloration with blue eyes, which only has pigment production at the cooler areas, the face, ears, paws, and tail; and the Tonkinese phenotypic variant, cbcs, which is an intermediate between the Burmese and Siamese. Several cat breeds are fixed for the albinism alleles, which include Burmese and Singapura for the cb allele, and Siamese, Birman and Himylayan for the cs allele.
Albino cats have been sporadically mentioned in the literature but quality photographs are not available nor has the phenotype been proven to be allelic to the color series (Turner et al., 1981). Also, blue-eyed versus pinked-eyed albino cats have not been clearly distinguished in published reports (Todd, 1977; Turner et al., 1981), thus it is unclear as to whether there are more than one complete albinism alleles in the cat, as has been reported for the mouse. Robinson (1973) suggested that albino cats would be an allele of TYR due to other species also showing the same phenotype with known mutations. Breeding experiments with Siamese type cats were attempted but did not produce an albino cat because the breeding study had to be terminated. Over 300 albino cats have been registered by the Cat Fanciers' Association (CFA) as a color variant of the Siamese.
In the United States there are approximately 50 cat breeds, some of which are hybrids with wildcat species and long-haired and short-haired varieties of the same breed. Not all breeds or colors are accepted by different cat fancy organizations, but basically there are four breeds (Siamese, Birman, Balinese and Javanese) that are fixed for “Siamese” points, and three breeds (Burmese, European Burmese and Singapura) that are fixed for the Burmese allele. Tonkinese cats are heterozygotes for these two alleles, hence matings produce cbcb Tonkinese, known as minks, and cscs Tonkinese that are known as color points. But due to the variations on pigment intensity due to environment, dilution factors of other genes and minor polygenic effects, distinguishing the variant of Tonkinese produced can be challenging for breeders.
Approximately thirteen breeds have desirable segregation for the cs and/or cb alleles but a few have these alleles in the gene pool but the color variants are not recognized. For example, Korats are recognized in only one color, blue, but cs segregates in this breed, producing undesirable “pointed” cats. This breed has a very limited population size, thus, the eradication of cats that have only a single gene that is undesirable, point-restriction, but many that contribute positively to the breed, could be very detrimental to the genetic diversity of the population. Hence, genetic tests for undesirable single gene traits could allow the continued management of the allele within the population, but through carrier testing, matings could be established that do not breed carrier to carrier, which would produced 25% undesirable cats.
Cat breeders fear undesirable traits, which quenches the enthusiasm for opening stud books and allowing the outcrossing of many domesticated breeds. Genetic testing for some of the undesirable traits, including albinism, can alleviate some of these fears and can promote better genetic diversity, increased heterozygosity, and hence possibly overall better health for companion animal breeds as well as animal breeds in captive breeding programs.
Thus, there is a need in the art for methods and compositions for testing for undesirable traits, including albinism. The present invention satisfies these and other needs.